Blood Ca2+ modulates responsiveness of renal 25(OH)D3-1 alpha-hydroxylase to PTH in rats

To clarify whether extracellular Ca2+ modulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1 alpha-hydroxylase, thyroparathyroidectomized rats were infused with 15 mM CaCl2, 20 mM EGTA, and/or 2.5 U/h parathyroid hormone (PTH), and blood Ca2+, serum 1,25-dihydroxyvitamin D [1,25(OH)2D], and renal 1 alpha-hydroxylase activity were determined. Rats with CaCl2, EGTA, or PTH infusion (group 1) exhibited low blood Ca2+, serum 1,25(OH)2D, and 1 alpha-hydroxylase activities. Infusion of CaCl2 alone (group 2) caused a significant increase in blood Ca2+ and a reduction in serum 1,25(OH)2D and 1 alpha-hydroxylase compared with group 1. Administration of PTH alone (group 3) markedly elevated blood Ca2+, serum 1,25(OH)2D, and 1 alpha-hydroxylase activity. When EGTA was infused along with PTH (group 4), blood Ca2+ was significantly reduced compared with group 3, and serum 1,25(OH)2D and renal 1 alpha-hydroxylase were further elevated. In contrast, when CaCl2 was infused with PTH (group 5), blood Ca2+ was higher than that in group 3, and serum 1,25(OH)2D and 1 alpha-hydroxylase activities were significantly reduced compared with group 3. No significant difference in serum inorganic phosphate or urinary cAMP excretion was observed by CaCl2 or EGTA infusion in both PTH-treated and nontreated rats. These results demonstrate that extracellular Ca2+ modulates the responsiveness of renal 1 alpha-hydroxylase to PTH as well as the base-line activity of the enzyme in the absence of PTH. These effects of extracellular Ca2+ on renal 1 alpha-hydroxylase may serve to offer an efficient way of regulating 1,25(OH)2D production and serum 1,25(OH)2D concentration by altering the responsiveness of 1 alpha-hydroxylase to PTH and possibly other stimulations depending on the demand for Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)